218 Neutrophil-specific defensin receptors that prevent skin dysbiosis and bacterial infection

Defensins are a large family of positively-charged antimicrobial peptides that have been implicated innate immunity. Although known for their ability to directly kill bacteria, the mechanisms by which defensins regulate host-pathogen interactions remain elusive. Herein, we deleted entire Defensin gene cluster (3 million base pairs) in keratinocyte-intrinsic manner and observed enhanced susceptibility infection with Staphylococcus aureus. Strikingly, identified previously unrecognized roles neutrophil-specific orphan G protein-coupled receptors, Mrgpra2a/b, as defensin receptors this context. Disruption defensin-Mrgpr axis resulted impaired epithelium mobilize neutrophils release IL-1β prevent skin dysbiosis S. aureus infection.